General Provisions Subpart A Scope The Quality System

Transcription

1 General Provisions Subpart A Scope The Quality System 20

2 Scope SCOPE (a) Applicability. (1) Current good manufacturing practice (CGMP) requirements are set forth in this quality system regulation. The requirements in this part govern the methods used in, and the facilities and controls used for, the design, manufacture, packaging, labeling, storage, installation, and servicing of all finished devices intended for human use. The requirements in this part are intended to ensure that finished devices will be safe and effective and otherwise in compliance with the Federal Food, Drug, and Cosmetic Act (the Act). This part establishes basic requirements applicable to manufacturers of finished medical devices. If a manufacturer engages in only some operations subject to the requirements in this part, and not in others, that manufacturer need only comply with those requirements applicable to the operations in which it is engaged. With respect to class I devices, design controls apply only to those devices listed in (a)(2). This regulation does not apply to manufacturers of components or parts of finished devices, but such manufacturers are 21

3 encouraged to use appropriate provisions of this regulation as guidance. Manufacturers of human blood and blood components are not subject to this part, but are subject to part 606 of this chapter. Manufacturers of human cells, tissues, and cellular and tissue-based products (HCT/Ps), as defined in (d) of this chapter, that are medical devices (subject to premarket review or notification, or exempt from notification, under an application submitted under the device provisions of the act or under a biological product license application under section 351 of the Public Health Service Act) are subject to this part and are also subject to the donoreligibility procedures set forth in part 1271 subpart C of this chapter and applicable current good tissue practice procedures in part 1271 subpart D of this chapter. In the event of a conflict between applicable regulations in part 1271 and in other parts of this chapter, the regulation specifically applicable to the device in question shall supersede the more general. (2) The provisions of this part shall be applicable to any finished device as defined in this part, intended for human use, that is manufactured, imported, or offered for import in any State or Territory of the United States, the District of Columbia, or the Commonwealth of Puerto Rico. (3) In this regulation the term "where appropriate" is used several times. When a requirement is qualified by "where appropriate," it is deemed to be "appropriate" unless the manufacturer can document justification 22

4 otherwise. A requirement is "appropriate" if nonimplementation could reasonably be expected to result in the product not meeting its specified requirements or the manufacturer not being able to carry out any necessary corrective action. (b) The quality system regulation in this part supplements regulations in other parts of this chapter except where explicitly stated otherwise. In the event of a conflict between applicable regulations in this part and in other parts of this chapter, the regulations specifically applicable to the device in question shall supersede any other generally applicable requirements. (c) Authority. Part 820 is established and issued under authority of sections 501, 502, 510, 513, 514, 515, 518, 519, 520, 522, 701, 704, 801, 803 of the act (21 U.S.C. 351, 352, 360, 360c, 360d, 360e, 360h, 360i, 360j, 360l, 371, 374, 381, 383). The failure to comply with any applicable provision in this part renders a device adulterated under section 501(h) of the act. Such a device, as well as any person responsible for the failure to comply, is subject to regulatory action. (d) Foreign manufacturers. If a manufacturer who offers devices for import into the United States refuses to permit or allow the completion of a Food and Drug Administration (FDA) inspection of the foreign facility for the purpose of determining compliance with this part, it shall appear for purposes of section 801(a) of the act, that the methods used in, and the 23

5 facilities and controls used for, the design, manufacture, packaging, labeling, storage, installation, or servicing of any devices produced at such facility that are offered for import into the United States do not conform to the requirements of section 520(f) of the act and this part and that the devices manufactured at that facility are adulterated under section 501(h) of the act. (e) Exemptions or variances. (1) Any person who wishes to petition for an exemption or variance from any device quality system requirement is subject to the requirements of section 520(f)(2) of the act. Petitions for an exemption or variance shall be submitted according to the procedures set forth in of this chapter, the FDA's administrative procedures. Guidance is available from the Food and Drug Administration, Center for Devices and Radiological Health, Division of Small Manufacturers, International and Consumer Assistance, New Hampshire Ave., Bldg. 66, rm. 4613, Silver Spring, MD , or , FAX: (2) FDA may initiate and grant a variance from any device quality system requirement when the agency determines that such variance is in the best interest of the public health. Such variance will remain in effect only so long as there remains a public health need for the device and the device would not likely be made sufficiently available without the variance Definitions (See Appendix A) 24

6 The regulations are initiated by the scope, which we initially discussed in chapter 1, but there some important elements to take from this. Firstly, the regulations take the approach not just of cgmp, but of the entire system that supports the realization of the product. This includes: the facilities, controls used for, the design, manufacture, packaging, labeling, storage, installation, and servicing of all finished devices. The requirements are intended to ensure that finished devices will be safe and effective and otherwise in compliance with the Federal Food, Drug, and Cosmetic Act (the act). These requirements apply to any organization which is manufacturing a finished medical device, but specifically excludes components. This can be a challenge for medical device manufacturers, as the onus of the device is on the finished device manufacturer and we'll see later (in Chapter 1 of Volume 2) the FDA refers to the manufacturer as the product owner, so as to ensure the product owner is not trying to transfer the quality of the product and the burden of regulatory compliance to a 25

7 Contract Manufacturing Organization (CMO) or a supplier. The second key point of the scope is that the manufacturer is required to comply with all of the regulations unless they document a specific rationale as to why a section is not appropriate. This is very common depending on the device being manufactured. For example, a manufacturer of a disposable syringe will not likely have a process for installation, but the rationale must be documented. Typically any exclusions to the regulations are documented in the quality manual. The third key point of the scope worth noting is the exemptions or variances as discussed in section (e) of the regulations. Exemptions and variances must be granted directly by the FDA and are typically done when there is a public health risk. As an example in 2009 there was a H1N1 swine flu pandemic and since there were no FDA-approved or cleared tests, the FDA allowed manufacturers of any H1N1 tests to apply to the FDA for an Emergency Use Authorization (EUA). During this declared public health emergency, manufacturers of H1N1 influenza virus tests that were unable to submit a complete premarket notification would be allowed to market their product upon an approval of an EUA from the FDA. The EUA's eventually expired, but this allowed a window of opportunity for some organizations to market their product without being in full compliance with the regulations. 26

8 The Quality System Quality System Each manufacturer shall establish and maintain a quality system that is appropriate for the specific medical device(s) designed or manufactured, and that meets the requirements of this part. Part requires the establishment of the quality system that is appropriate for the medical device being manufactured. The quality system can vary depending on the organization, but as a recommended system structure Figure 2 is a good place to start. Figure 2 is a modified version of the diagram in the FDA's guidance on Quality System Inspection Techniques (QSIT)2. The Quality System (QS) defines which parts of 21CFR820 are relevant, which might be exempt, how these processes interact and the key documents that define the system for the organization. A simple diagram showing the key systems and how the relate to one another is typically used to define the QS. While it's not required in the regulations, a quality manual is usually established as the organization's foundation and road map to the quality system. 27

9 Medical Device Reporting Reports of Corrections & Removals Medical Device Tracking Corrective & Preventative Actions Facility & Equipment Controls Design Controls Management Production & Process Controls Material Controls Document / Records & Change Control Sterilization Process Control Figure 2. Diagram of the seven quality sub-systems. The major subsystems are outlined in black and the satellite subsystems outlined in blue. This diagram is based on the diagram from FDA guidance on QSIT (Quality System Inspection Technique) and will vary somewhat depending on the organization. This image is offered as a good reference to start with and modify as needed. The major quality systems are: Corrective and Preventative Actions (CAPA), with it's satellites, Production and Process Controls, with it's satellite of sterilization (if applicable), 28

10 Management System, Design Control. Any audit from the FDA will review these major subsystems. There is also an evolution currently happening where The Quality System Inspection Technique (QSIT) guide is currently being revised as the FDA has come to realize that many medical device manufacturers have simply become assembly houses and are not actually manufacturing many of their critical components. Since this has become evident, this guidance is being revised to add additional emphasis around supplier management (See Chapter 1 of Volume 2 for more detail). It is likely in the revised QSIT guidance that supplier management will become a more critical subsystem, and will get added to the list of major subcomponents. Supplier management typically would fall under, the Material Control subsystem. 29

11 Quality System Requirements Subpart B Management Responsibility Quality Policy Organizational Structure Management Representative Management Review Quality Planning Quality Audits Personnel Training 30

12 Management Responsibility Management Responsibility (a) Quality policy. Management with executive responsibility shall establish its policy and objectives for, and commitment to, Quality. Management with executive responsibility shall ensure that the quality policy is understood, implemented, and maintained at all levels of the organization. (b) Organization. Each manufacturer shall establish and maintain an adequate organizational structure to ensure that devices are designed and produced in accordance with the requirements of this part. (1) Responsibility and authority. Each manufacturer shall establish the appropriate responsibility, authority, and interrelation of all personnel who manage, perform, and assess work affecting quality, and provide the independence and authority necessary to perform these tasks. (2) Resources. Each manufacturer shall provide adequate resources, including the assignment of trained personnel, for management, 31

13 performance of work, and assessment activities, including internal quality audits, to meet the requirements of this part. (3) Management representative. Management with executive responsibility shall appoint, and document such appointment of, a member of management who, irrespective of other responsibilities, shall have established authority over and responsibility for: (i) Ensuring that quality system requirements are effectively established and effectively maintained in accordance with this part; and (ii) Reporting on the performance of the quality system to management with executive responsibility for review. (c) Management review. Management with executive responsibility shall review the suitability and effectiveness of the quality system at defined intervals and with sufficient frequency according to established procedures to ensure that the quality system satisfies the requirements of this part and the manufacturer's established quality policy and objectives. The dates and results of quality system reviews shall be documented. (d) Quality planning. Each manufacturer shall establish a quality plan which defines the quality practices, resources, and activities relevant to devices that are designed and manufactured. The manufacturer shall 32

14 establish how the requirements for quality will be met. (e) Quality system procedures. Each manufacturer shall establish quality system procedures and instructions. An outline of the structure of the documentation used in the quality system shall be established where appropriate. This section of the regulations establishes the foundation for the organizations Quality Management System (QMS). It's of note that the regulations don't require a quality manual, however, the ISO standard for medical devices (ISO 13485)4 does and the regulations say to establish which means there needs to be documented evidence of the established quality system, which is almost always done in the form of a quality manual. Typically the Quality Manual mirrors the regulations (much like this book) so that each subsection of the regulation is a major section of the quality manual. The QMS is the hub of the quality system and will always be evaluated in an audit by the FDA. 33